Boosting Immunity for the Long Term

Boosting Immunity for the Long Term

Vaccines take advantage of a remarkable ability of our immune system: it can remember viral infections for years, even decades, after they have first been encountered and defeated. While each individual antibody we make lasts only about a month, we retain the means of making that individual antibody for a lifetime, with rare exceptions.

Until now, the exact mechanism behind this was poorly understood, but researchers at The Wistar Institute have discovered some of the protein signals responsible for keeping the memory of distant viral infections alive within our bodies. Their research may aid scientists in creating better, more effective vaccines for diseases like influenza.

“We are particularly interested in how our bodies generate antibodies against viruses and how we maintain anti-viral antibody secreting cells as a hedge against future infection from the same virus,” said Jan Erikson, Ph.D., senior author of the study, professor in the Tumor Microenvironment and Metastasis Program and a member of The Wistar Vaccine Center. “We know protein signals sustain the cells that make antibodies against viruses in perpetuity, which we believe is crucial knowledge for the development of vaccines for lasting protection.”

The main role of vaccines is to stimulate the production of antibodies that bind to portions of the infectious agent. Once bound, the antibodies provide a target for the immune system, allowing immune cells to attack it or any infected cells in order to clear away disease.

Antibodies are highly variable proteins that are produced in huge quantities by a subset of white blood cells, called B cells, that have transformed into antibody factories, termed antibody secreting cells (ASCs). Our immune system produces a broad array of antibodies, but during an infection with a virus, for example, the immune system allows the predominant production of antibodies that are directed against the virus. The cells making these particular antibodies are then selected for preservation.

According to Erikson and her colleagues, this act of preservation — essentially immune memory — requires signals, provided by proteins called BLyS and APRIL. Mice that have been exposed to influenza require these proteins in order to sustain anti-influenza ASCs in their lungs. The researchers found that neutralizing BLyS and APRIL reduced the numbers of anti-viral ASCs found in the lungs and bone marrow, yet interestingly, did not affect the ASCs found in the spleen or in lymph nodes near the lungs.

BLyS and APRIL bind to another protein called TACI, a receptor found on the surface of ASCs, which the researchers see as an important translator for marking the ASCs that will become long-lived.

“Our studies show that mice that lack TACI can mount an initial B cell response to viral infection — and are able to produce antibodies to influenza — but these mice fail to maintain anti-viral ASCs over a long period of time,” said Amaya I. Wolf, Ph.D., the study’s lead author anda postdoctoral fellow in the Erikson laboratory. “Importantly, we show that this results in lower anti-viral antibody levels, and mice are less protected against a secondary viral attack at a later time.”

According to Wolf, it might be possible to manipulate ASC behavior to prolong or strengthen the effectiveness of vaccines to viral diseases, such as influenza. Drugs that induce targeted release of ASC survival factors, such as BLyS and APRIL, could theoretically help to maintain the production of specific antibodies, making for a more effective flu vaccine. While the seasonal flu is constantly mutating — necessitating an annual vaccine — even weakly reactive antibodies could be protective if there are enough of them and if the immune system can retain the memory to produce them over the long-term.

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Featured Image: Horner Brass Microscope

The microscope in the image belonged to William E. Horner, M.D., a collaborator with Caspar Wistar, M.D., in the early 1800s.

Dr. Horner, a lecturer at the University of Pennsylvania, was a pioneer of the use of microscopes in anatomical and medical research. He authored Special Anatomy and Histology, a seminal text on the subject.